Serum Parathyroid Hormone but Not Vitamin D Is Associated with Impaired Gait in Community‐Dwelling Older Adults

To the Editor: Vitamin D deficiency has been associated with poor physical performance, muscle weakness, falls, and fractures.1 Previous studies have shown that high parathyroid hormone (PTH) is also associated with greater falls risk, suggesting a deleterious effect on neuromuscular function independent of vitamin D concentrations.2, 3 Although vitamin D supplementation can improve balance, its effect on gait performance is not well established.4 In addition, the associations between PTH and gait parameters have not been examined. The aim of this study was to evaluate the association between vitamin D and PTH serum levels on spatiotemporal measures of gait and balance as accepted markers of fall risk in a sample of community-dwelling older adults. This was a cross-sectional analysis of baseline data from the Vitamin D and Mobility Study.5 The University of Western Ontario Ethical Review Board approved the study, and written informed consent was obtained at enrollment. Venous blood samples were collected for the measurement of serum 25(OH) vitamin D and intact PTH (iPTH). Specimens were stored at −82°C as aliquots immediately after centrifugation. Serum 25(OH) Vitamin D was measured using a specific radioimmunoassay (Diasorin Inc., Sallugia, Italy). Serum iPTH levels were determined using a two-site chemiluminescent enzyme-linked immunosorbent assay (Alpco Ltd, Salem, NH; range 10–55 pg/mL, sensitivity 1.57 pg/mL). Gait performance was evaluated at usual pace on an electronic walkway system (GaitRITE, CIR Systems, Inc., Peekskill, NY). A force platform (Bertec Corp., Columbus, OH) was used for the Modified Clinical Test for Sensory Integration in Balance to measure total sway area (cm2). Total sway areas were normalized using a natural log transformation because of a lack of normal distribution (n = 72). Pearson correlations and multivariable linear regression models were used to evaluate the effect of relationship between serum 25(OH) vitamin D levels and PTH on gait and balance, adjusted for age, sex, comorbidities, number of medications, years of education, body mass index (BMI), and Mini-Mental State Examination (MMSE) score. Significance was set at a P < .05. All statistics were performed using SPSS version 23 (SPSS, Inc., Chicago, IL). Eighty-one community-dwelling older adults (mean age 80.9 ± 6.9, 64% female) with high functionality (Lawton-Brody instrumental activity of daily living score 7.5 ± 1.3 out of 8) were included. Mean BMI was 26.0 ± 4.2 kg/m2, mean MMSE score was 27.3 ± 4.2, and mean gait velocity was 94.3 ± 14 cm/s. Renal function, assessed according to estimated glomerular filtration rate (mean 74.7 ml/min per 1.73 m2), and elemental calcium serum levels (mean 2.24 mmol/L) were normal in all participants. None of the participants was vitamin D deficient (<10 ng/L), 16.0% were insufficient (10–20 ng/L), 21.0% were sufficient (21–30 ng/L), and 63.0% had levels greater than 30 ng/L. High PTH serum levels (>55 pg/mL) were found in 30.9% of participants. Higher PTH was inversely correlated with vitamin D levels (correlation coefficient = −0.343, P < .001). Vitamin D serum concentrations were not associated with gait and balance performance. Significant correlations were found between high PTH levels, poor gait performance (Figure 1), and balance displacement. Specifically, high PTH serum levels were associated with mean gait stride time (duration of a stride, β = 0.34, 95% CI = 27.9–166.5, P = .007), stride time variability (β = 0.29, 95% CI = 0.4–4.0, P = .02), mean double support time (duration of both feet in contact with floor during walking, β = 0.30, 95% CI = 11.4–111.8, P = .02), stride velocity variability (β = 0.26, 95% CI = 0.3–4.4, P = .02), and balance displacement under rigid surface with eyes closed (β = 0.27, 95% CI = 0.009–0.53, P = .04). These relationships remained significant after controlling for important confounders, including age, sex, number of medications, years of education, BMI, MMSE, and vitamin D levels. Higher PTH levels, in the absence of primary hyperparathyroidism, were associated with poor gait and balance performance independent of vitamin D serum levels. None of the participants was deficient in vitamin D, and only 16% were insufficient, which may explain the lack of association between vitamin D and gait and balance impairments in the sample. These findings may explain the known effect of PTH on falls risk, suggesting that gait and balance impairment can mediate it.6 The association between PTH and gait velocity and variability, both robust markers of fall risk,7, 8 seems to be independent of confounders including comorbidities, obesity, cognition, and serum vitamin D levels. PTH may affect muscle function through several biological mechanisms, including increasing protein catabolism and decreasing the number of type 2 muscle fibers and mitochondrial oxygen uptake,9 all of which can ultimately impair gait and balance performance. Because of the cross-sectional design, a causal association between serum PTH and gait and balance performance was not determined, although the association is biologically plausible. High serum PTH levels were independently associated with slow gait, high gait variability, and impaired balance in this sample of community-dwelling older adults. High serum PTH levels may have a deleterious neuromuscular action independent of vitamin D serum levels. Further investigation aimed at understanding the underlying mechanism for these associations is needed. Conflict of Interest: This study was funded by an operating grant from the CIHR (MOP 122211). Dr. Montero-Odasso is supported by grants from the Canadian Institutes for Health and Research (CIHR)—Institute of Aging, The Drummond Foundation, The Physician Services Incorporated Foundation of Canada, The Lawson Health Research Institute, The Ontario Ministry of Research and Innovation, and Western University Department of Medicine, Program of Experimental Medicine. He is the first recipient of the Schulich Clinician-Scientist Award and recipient of the CIHR New Investigator Award. He has no relevant financial interest in this manuscript. Author Contributions: MMO has full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. Study concept and design: MMO. Acquisition of subjects and/or data: MMO, SMH, AI. Analysis and interpretation of data: MMO, SMH, RS, TD, GD, RC. Preparation/Critical review of manuscript: MMO, RS, AI, TD, GD, SMH, RC. Obtained funding: MMO. Statistical expertise: SMH, RS, MMO. Study supervision: MMO. Sponsor's Role: None.

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